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Phosphate ion channels in sarcoplasmic reticulum of rabbit skeletal muscle

Derek R. Laver, Gerlinde K. E. Lenz and Angela F. Dulhunty *

1. Phosphate ions (P_i) enter intracellular Ca²⁺ stores and precipitate Ca²⁺. Since transport pathways for P_i across the membrane of intracellular calcium stores have not been identified and anion channels could provide such a pathway, we have examined the P_i conductance of single anion channels from the sarcoplasmic reticulum (SR) of rabbit skeletal muscle using the lipid bilayer technique.
2. Two anion channels in skeletal muscle SR, the small conductance (SCl) and big conductance (BCl) chloride channels, were both found to have a P_i conductance of 10 pS in 50 mM P_i. The SCl channel is a divalent anion channel which can pass HPO₄^2- as well as SO₄^2- (60 pS in 100 mM free SO₄^2-). The BCl channel is primarily a monovalent anion channel. The SCl and BCl channels are permeable to a number of small monovalent anions, showing minor selectivity between Cl^-, I^- and Br^- (Cl^- > I^- > Br^-) and relative impermeability to cations and large polyatomic anions (Cs⁺, Na⁺, choline⁺, Tris⁺, Hepes^- and CH₃O₃S^-).
3. The P_i conductance of SCl and BCl channels suggests that both channel types could sustain the observed P_i fluxes across the SR membrane. Comparison of the blocking effects of the phosphonocarboxylic acids, ATP and DIDS, on the anion channels with their effects on P_i transport suggests that the SCl channel is the more likely candidate for the SR P_i transport mechanism.
4. The SCl channel, with previously unknown function, provides a regulated pathway for P_i across the SR membrane which would promote P_i entry and thereby changes in the rapidly releasable Ca²⁺ store during onset and recovery from muscle fatigue. Anion channels may provide a pathway for P_i movement into and out of Ca²⁺ stores in general.

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